Chronic fatigue syndrome (CFS) is a serious health problem in the United States. It is estimated that the prevalence rate in the United States is as much as 250/100,000 persons. No specific treatment has been identified. Recent observations suggest a strong association between CFS and a treatable disorder in the regulation of blood pressure known as neurally-mediated hypotension (NMH). In small unblinded studies, treatment with fludrocortisone and other medications directed against NMH has appeared to be beneficial, with 40% of treated patients reporting an almost complete resolution of symptoms and another 30% reporting some improvement. The specific aim of this randomized double blind, placebo-controlled trial is to determine whether fludrocortisone is efficacious for those with CFS. In this study, we randomized 100 adults with CFS and NMH, as defined by abnormal responses to postural challenge (tilt table test), to receive either fludrocortisone or placebo. The participants completed self-assessment forms on mood, energy, activity, and performance. The primary indicator of efficacy is a 15-point improvement (on a scale of 1 to 100) in the general sense of well being score. All subjects were 18-49 years of age who satisfy the 1994 CDC criteria for CFS, had undergone a medical evaluation to exclude other causes of CFS, and had hypotension provoked during stage 1 or 2 of an upright tilt table test. Together with our collaborators at Johns Hopkins, we screened 171 subjects, finding 62% of them to have abnormal tilt tests. All 100 eligible subjects were enrolled. The blinded treatment was well tolerated with no serious adverse reactions, nor concerns of our Data and Safety Monitoring Board. The study data were analyzed and were reported at the American College of Cardiology annual scientific meeting in March, 2000. The work has been submitted for publication. The study is, otherwise, terminated.